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Engineered reporter phages for detection of Escherichia coli, Enterococcus, and Klebsiella in urine
The rapid detection and species-level differentiation of bacterial pathogens facilitates antibiotic stewardship and improves disease management. Here, we develop a rapid bacteriophage-based diagnostic assay to detect the most prevalent pathogens causing urinary tract infections: Escherichia coli, En...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10359277/ https://www.ncbi.nlm.nih.gov/pubmed/37474554 http://dx.doi.org/10.1038/s41467-023-39863-x |
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author | Meile, Susanne Du, Jiemin Staubli, Samuel Grossmann, Sebastian Koliwer-Brandl, Hendrik Piffaretti, Pietro Leitner, Lorenz Matter, Cassandra I. Baggenstos, Jasmin Hunold, Laura Milek, Sonja Guebeli, Christian Kozomara-Hocke, Marko Neumeier, Vera Botteon, Angela Klumpp, Jochen Marschall, Jonas McCallin, Shawna Zbinden, Reinhard Kessler, Thomas M. Loessner, Martin J. Dunne, Matthew Kilcher, Samuel |
author_facet | Meile, Susanne Du, Jiemin Staubli, Samuel Grossmann, Sebastian Koliwer-Brandl, Hendrik Piffaretti, Pietro Leitner, Lorenz Matter, Cassandra I. Baggenstos, Jasmin Hunold, Laura Milek, Sonja Guebeli, Christian Kozomara-Hocke, Marko Neumeier, Vera Botteon, Angela Klumpp, Jochen Marschall, Jonas McCallin, Shawna Zbinden, Reinhard Kessler, Thomas M. Loessner, Martin J. Dunne, Matthew Kilcher, Samuel |
author_sort | Meile, Susanne |
collection | PubMed |
description | The rapid detection and species-level differentiation of bacterial pathogens facilitates antibiotic stewardship and improves disease management. Here, we develop a rapid bacteriophage-based diagnostic assay to detect the most prevalent pathogens causing urinary tract infections: Escherichia coli, Enterococcus spp., and Klebsiella spp. For each uropathogen, two virulent phages were genetically engineered to express a nanoluciferase reporter gene upon host infection. Using 206 patient urine samples, reporter phage-induced bioluminescence was quantified to identify bacteriuria and the assay was benchmarked against conventional urinalysis. Overall, E. coli, Enterococcus spp., and Klebsiella spp. were each detected with high sensitivity (68%, 78%, 87%), specificity (99%, 99%, 99%), and accuracy (90%, 94%, 98%) at a resolution of ≥10(3) CFU/ml within 5 h. We further demonstrate how bioluminescence in urine can be used to predict phage antibacterial activity, demonstrating the future potential of reporter phages as companion diagnostics that guide patient-phage matching prior to therapeutic phage application. |
format | Online Article Text |
id | pubmed-10359277 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-103592772023-07-22 Engineered reporter phages for detection of Escherichia coli, Enterococcus, and Klebsiella in urine Meile, Susanne Du, Jiemin Staubli, Samuel Grossmann, Sebastian Koliwer-Brandl, Hendrik Piffaretti, Pietro Leitner, Lorenz Matter, Cassandra I. Baggenstos, Jasmin Hunold, Laura Milek, Sonja Guebeli, Christian Kozomara-Hocke, Marko Neumeier, Vera Botteon, Angela Klumpp, Jochen Marschall, Jonas McCallin, Shawna Zbinden, Reinhard Kessler, Thomas M. Loessner, Martin J. Dunne, Matthew Kilcher, Samuel Nat Commun Article The rapid detection and species-level differentiation of bacterial pathogens facilitates antibiotic stewardship and improves disease management. Here, we develop a rapid bacteriophage-based diagnostic assay to detect the most prevalent pathogens causing urinary tract infections: Escherichia coli, Enterococcus spp., and Klebsiella spp. For each uropathogen, two virulent phages were genetically engineered to express a nanoluciferase reporter gene upon host infection. Using 206 patient urine samples, reporter phage-induced bioluminescence was quantified to identify bacteriuria and the assay was benchmarked against conventional urinalysis. Overall, E. coli, Enterococcus spp., and Klebsiella spp. were each detected with high sensitivity (68%, 78%, 87%), specificity (99%, 99%, 99%), and accuracy (90%, 94%, 98%) at a resolution of ≥10(3) CFU/ml within 5 h. We further demonstrate how bioluminescence in urine can be used to predict phage antibacterial activity, demonstrating the future potential of reporter phages as companion diagnostics that guide patient-phage matching prior to therapeutic phage application. Nature Publishing Group UK 2023-07-20 /pmc/articles/PMC10359277/ /pubmed/37474554 http://dx.doi.org/10.1038/s41467-023-39863-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Meile, Susanne Du, Jiemin Staubli, Samuel Grossmann, Sebastian Koliwer-Brandl, Hendrik Piffaretti, Pietro Leitner, Lorenz Matter, Cassandra I. Baggenstos, Jasmin Hunold, Laura Milek, Sonja Guebeli, Christian Kozomara-Hocke, Marko Neumeier, Vera Botteon, Angela Klumpp, Jochen Marschall, Jonas McCallin, Shawna Zbinden, Reinhard Kessler, Thomas M. Loessner, Martin J. Dunne, Matthew Kilcher, Samuel Engineered reporter phages for detection of Escherichia coli, Enterococcus, and Klebsiella in urine |
title | Engineered reporter phages for detection of Escherichia coli, Enterococcus, and Klebsiella in urine |
title_full | Engineered reporter phages for detection of Escherichia coli, Enterococcus, and Klebsiella in urine |
title_fullStr | Engineered reporter phages for detection of Escherichia coli, Enterococcus, and Klebsiella in urine |
title_full_unstemmed | Engineered reporter phages for detection of Escherichia coli, Enterococcus, and Klebsiella in urine |
title_short | Engineered reporter phages for detection of Escherichia coli, Enterococcus, and Klebsiella in urine |
title_sort | engineered reporter phages for detection of escherichia coli, enterococcus, and klebsiella in urine |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10359277/ https://www.ncbi.nlm.nih.gov/pubmed/37474554 http://dx.doi.org/10.1038/s41467-023-39863-x |
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